The terrorist threat is very real, and it's about to get worse.
Scientists should concern themselves before it's too late

For half a century America has participated with the world's nuclear
powers in an uneasy standoff of mutually assured destruction. Despite
the seemingly relentless proliferation of nuclear arms, there's reason
to hope that some version of the current stalemate will continue to
hold. Against this backdrop, terrorist factions and "nations of
concern" (the current government euphemism for rogue states) have
sought ways to leverage their chances. In the jargon of the day, they
seek a means to wage "asymmetric warfare" against a more
powerful, nuclear-capable adversary Asymmetric warfare concentrates on
the use of unconventional (and affordable) weapons and tactics, ranging
from traditional guerrilla fighting to the deployment of new weapons of
mass destruction. Ironically, the supremacy in conventional weaponry
established by the U.S.--and demonstrated to lethal effect during the
1991 Gulf War--has made asymmetric warfare all the more attractive.
Figuring prominently in the arsenal of asymmetric warfare are both
biological and chemical weapons. Although it may be something of a
misnomer to label most current forms of these agents as "weapons of
mass destruction," their power is nevertheless considerable. Worse
still, it is now increasing, and these weapons are emerging as a serious
threat to peace in the 21st century Here I explore the historical
development and use of biological weapons, as well as some recent trends
in their evolution and the prospects for containing their proliferation.

The Plague and Anthrax

Biological warfare is not a new phenomenon. The ancient Romans, and
others before them, threw carrion into wells to poison their
adversaries' drinking water. In the 14th century the Tatars catapulted
the bodies of bubonicplague victims over the city walls of Kaffa, a
Black Sea port that served as a gateway to the Silk Road trade route.
People inside the city soon came down with the disease, suggesting that
the maneuver may have worked--but the tactic may have exceeded the
Tatars' operational goals. Some of the city's inhabitants escaped in
sailing ships, which happened to be infested with rats, carrying fleas
infected with the causative agent of plague, the bacterium Yersinia
pestis. The escaping ships entered various Italian ports that
subsequently served as foci for the spread of the disease. Over the next
three years, the bubonic plague--the Black Death--raged northward,
wiping out nearly a third of Western Europe.

It was not until the 19th century that the microbial basis for
infectious disease was understood. One of the first illnesses to be
explained by the new germ theory was anthrax, an infectious disease
common to sheep and cattle. Indeed, the primary architects of the germ
theory--Robert Koch, Louis Pasteur and Joseph Lister--were instrumental
in describing anthrax and its containment. Koch was the first to isolate
and describe the anthrax bacterium (Bacillus anthracis). Pasteur
developed the first animal vaccine against anthrax, which, together with
Lister's ideas about antiseptic precautions, helped turn the tide
against outbreaks of the disease.

Anthrax is only weakly communicable in humans and rarely causes
disease, unless the bacterium comes into contact with the bloodstream
through a wound (causing cutaneous anthrax) or is ingested in
contaminated meat (resulting in intestinal anthrax). However, Bacillus
anthracis has the ability to form resistant spores, which can remain
viable for over a hundred years if kept desiccated and out of direct
sunlight. Breathing in significant numbers of spores (typically
estimated at about 10,000) can lead to inhalation anthrax in humans,
which was historically called "woolsorter's disease" because
spores were prevalent in the contaminated wool of sheep in 19th-century
England. Inhalation anthrax is a very deadly disease in humans. Unless
treated with large doses of a penicillin-type antibiotic within the
first day or so of exposure it has a mortality rate in excess of 80
percent. This is to be contrasted with smallpox, which has a mortality
rate of "only" around 30 percent. Only some filoviruses, such
as Ebola, wh ich cause hemorrhagic fevers, have comparable rates of
mortality.

All of this suggests why Bacillus anthracis became the agent of
choice for most biological warfare programs. Consider the properties of
anthrax. It is convenient: Variants of the anthrax bacterium can be
isolated worldwide (although not all possess equal virulence), and great
quantities of spores can be readily prepared from liquid cultures. It is
robust: Once desiccated and stabilized, hardy spores have a long shelf
life and are well suited to weaponization in a device that can deliver a
widespread aerosol. It is self- terminating: Airborne spores remain
infectious until they fall to the ground, where most become inactivated
by sunlight. It is effective: After inhalation the spores produce
disease with a high mortality and morbidity. It can be contained:
Anthrax is not very communicable, thereby reducing the risk that it will
spread beyond the intended target. Moreover, a well-established vaccine
exists that can prevent the onset of the disease, allowing it to be used
safely by the aggressor. This is a two- edged sword, of course, since
the vaccine may be available to the target population as well. For this
reason alone, anthrax doesn't quite qualify as the perfect bioweapon.

There are certain other drawbacks to anthrax as a weapon. The number
of spores that must be delivered to the lungs to produce the disease is
quite high compared with some other infectious agents--it has been
estimated that certain viruses and rickettsiae may communicate disease
with just a single particle. Finally, for conventional anthrax,
antibiotic treatment can be effective if administered quickly. Even so,
of all the natural biowarfare agents, anthrax traditionally ranks near
the top of everyone's short list.

The World Wars

The First World War saw one of the first attempts to use anthrax
during warfare, directed-ineffectively--against animal populations.
Instead, WWI became infamous for its introduction of poisonous mustard
gas, which was used effectively against humans. (By odd coincidence, WWI
also overlapped with a deadly outbreak of influenza, the Great Pandemic
of 1918, which eventually killed more people than the Great War itself.)
International revulsion at the horrors of WWI led to the signing of the
Geneva Protocol of 1925, which went into force on February 8, 1928, with
29 participating nations, including the U.S. The treaty contained
"A Protocol for the Prohibition of the Use in War of Asphyxiating
gas, and of Bacteriological Methods of Warfare."

Although the Geneva Protocol didn't expressly forbid the production
and development of biological weaponry, it did ban all use during war.
Disappointingly, neither the U.S. nor Japan ratified the treaty before
the advent of World War II, when anthrax and other bioweapons were
secretly being developed by both countries--as well as by Germany, the
U.S.S.R. and Great Britain. The Japanese and British bioweapons programs
were particularly extensive, but no documented use of agents ever
occurred during combat. This may have been due to residual respect for
the 1925 treaty or, what seems more likely, from the relative immaturity
and associated imperfections of bioweapons technology.

There were some notorious instances of biological warfare during this
period, however. The Japanese Military Unit 731 at Ping Fan, Manchuria,
experimented extensively with bioweapons, killing thousands of prisoners
of war with anthrax, cholera, plague, dysentery and other infectious
agents. They also released plague on the Chinese civilian population of
Chekiang Province on several occasions by dropping from airplanes
laboratory-grown fleas fed on infected rats. The Soviets may have
deliberately infected German Panzer troops with tularemia during the
Battle of Stalingrad in 1942, by far the costliest battle of WWII, but
the ensuing outbreak soon spread to both sides and resulted in more than
100,000 cases of the disease.

Unlike the years following WWI, the post-WWII period heard little
public debate concerning the need to limit bioweapons--perhaps owing to
the global preoccupation with nuclear arms that began in 1945. With the
advent of the Cold War, the U.S. biowarfare program (begun in 1942 and
aided by postwar intelligence from the Japanese) went into overdrive.
Over the course of the next 25 years, the U.S. would quietly develop,
test and weaponize at least 10 different biowarfare agents, including
bacteria, viruses and microbe-derived toxins. The U.S. not only
experimented with human disease, but also targeted economically vital
agriculture with fungal weapons such as wheat rust and rice blast. The
Soviets had a program that was every bit a match for the American one,
but concentrated on a different subset of diseases. Both countries
stockpiled plenty of anthrax.

A good deal of effort on both sides went into attacking the problem
of weaponization. Biowarfare agents may be deadly, but they are also
labile and difficult to deliver to the intended target. It took years of
experimentation before the U.S. and Soviet programs eventually succeeded
in developing effective means of stabilization and distribution--in the
form of explosive bomblets or aerosol-spray weapons that could be
delivered by aircraft or ballistic missiles. Today, the operating
principles of such delivery devices are among the most closely held
national secrets. This is entirely appropriate, given the relative ease
with which most other aspects of the bioweapons problem are tackled.

Modern-Day Transgressions

On November 25, 1969, under President Nixon, the U.S. announced that
it would unilaterally and unconditionally renounce all biological
weapons. Following executive order, the U.S. program was summarily
terminated, and the Department of Defense was instructed to destroy all
remaining stockpiles of weapons based on biological agents. This order
was extended the following year to cover toxin weapons, including
biologically produced toxins. The existing American stockpiles of
biological weapons were destroyed between May 1971 and May 1972.

These welcome developments paved the way for the landmark
international treaty of April 10, 1972, the Biological and Toxin Weapons
Convention (or BWC)--which has now been signed by 160 nations and
ratified by 143. Among the countries that have signed and ratified the
treaty are the U.S., Great Britain, China, the Russian Federation, Iraq,
Iran, Libya and North Korea--some of which figure prominently in reports
of actual or suspected bioweapons programs. Eighteen nations signed the
treaty but subsequently failed to ratify it--including Egypt, Syria and
Somalia--and 34 nations haven't even signed it, including Israel.

The BWC, which went into force in March 1975, took ambitious steps to
ban both biological and chemical weapons, including their development,
production, procurement or stockpiling for any hostile purpose or use m
armed conflict. Unfortunately, the BWC incorporated no provisions to
investigate or follow up on suspicious activities. It lacked
"teeth."

Perhaps the greatest BWC transgression of all occurred between 1972
and 1992, when a truly massive bioweapons effort was under way in the
Soviet Union. Despite endorsing the BWC Treaty, the Soviet Union carried
out ultra-secret bioweapons work right up until it collapsed in 1990.
Some experts contend that a low, but significant, level of research
still exists today. Revelations of the staggering scope of the Soviet
program have only recently come to light, after the much-publicized
defection of Ken Alibek--formerly Colonel Kanatjan Alibekov--the Deputy
Director of Biopreparat, the Soviet state "pharmaceutical"
agency charged with carrying Out bioweapons research.

Alibek has called Biopreparat "the darkest conspiracy of the
cold war" and tells a chilling tale. During the heyday of the
Soviet program, Alibek supervised as many as 32,000 people (out of
60,000 in the program) at nearly 40 facilities spread throughout the
Soviet Union--effectively a "toxic archipelago." Here the
Soviets worked not only on perfecting "conventional"
biological weapons based on anthrax, glanders and plague, but also on
weaponizing deadly (and highly contagious) viruses such as smallpox,
Marburg and Ebola. In contrast to the American bioweapons effort, the
Soviets considered the best bioweapons agents to be those for which
there was no prevention and no cure.

It was during Biopreparat's heyday, in 1979, that the "Sverdlovsk
incident" occurred. In April and May of that year, about 100 people
and uncounted livestock suddenly died of anthrax in Sverdlovsk (now
Yekaterinburg), a city of 1.2 million people. All the victims were
located within a narrow band directly downwind of a secure
microbiological facility run by the military. The Soviet authorities
blamed the deaths on contaminated meat (intestinal anthrax), whereas
U.S. agencies attributed the deaths to inhalation anthrax. The latter
explanation would constitute prima facie evidence for violation of the
BWC. International investigations followed, some involving noted Harvard
biologist Matthew Meselson. His group's reports, although somewhat
critical, initially seemed to lend credence to the Soviet explanation.
However, subsequent findings and detailed witness accounts left little
room for doubt.

Today, it appears that the deaths were precipitated by a shift worker
at the microbiological installation who removed a critical filter that
had clogged. The filter happened to be on the output of a drying machine
used to remove liquid from industrial-scale cultures of anthrax spores,
which were being produced for bioweapons. An aerosol of spores was
released from the unit's exhaust pipes over a period of several hours
before the mistake was discovered. Sverdlovsk suffered the single
largest epidemic of inhalation anthrax in history. In 1992, former
Russian President Boris Yeltsin formally acknowledged the true origin of
the outbreak.

The current economic and political climate in the former Soviet Union
raises the disturbing likelihood that their bioweapons experts will be
forced to seek employment elsewhere, resulting in unwelcome
proliferation. The analogous problem arises for former Soviet nuclear
experts, of course, but bioweapons issues have received comparatively
little attention and scant resources.

The BWC was also clearly violated by Iraq, which established
extensive programs for the development of both chemical and biological
weapons under Saddam Hussein in the early 1980s. Details of these
programs only surfaced in the wake of the Gulf War, following
investigations conducted by the United Nations Special Commission (UNSCOM)
in charge of Iraqi disarmament. As a result of these investigations,
more is known today about the once-secret bioweapons program in Iraq
than that of almost any other nation. Iraq maintained several distinct
facilities, including those at the Muthanna State Establishment (the
principal chemical weapons plant), Salman Pak (the main biowarfare
research center, just south of Baghdad), the "Single-Cell Protein
Production Plant" at Al Hakam (the main bioweapons production
facility, allegedly built to produce animal feed) and the Foot and Mouth
Disease Center at Al Manal (a site for biowarfare research on viruses).

The Al Hakam facility began mass production of weapons-grade anthrax
in 1989 and eventually generated at least 8,000 liters (based on
declared amounts). This plant was not bombed during the Gulf War in
1991, and its true role in Iraq's bioweapons program was not established
until 1995, at which point the U.N. ordered its destruction. Relevant
portions of the facilities at Salman Pak and Al Manal were also
destroyed, either by the Iraqis themselves or under direct UNSCOM
supervision.

In the aftermath of the Gulf War, Iraq officially acknowledged that
it had worked with several species of bacterial pathogen--including
Bacillus anthracis, Clostridium botulinum and Clostridium perfringens
(which causes gas gangrene)--and several viruses--including enterovirus
17 (human conjunctivitis), rotavirus and camel pox. They also purified
biological toxins, including botulinum toxin, ricin and aflatoxin. In
total, a half million liters of biological agents were grown.

A Meaningful Bioweapons Treaty

All told, it's suspected that more than a dozen sovereign nations
possess some form of offensive bioweapons program, assuming one includes
some republics of the former Soviet Union. How can this proliferation be
controlled? One approach is to muster international resources to enhance
and strengthen the provisions of the BWC--giving it some
"teeth." This would include verification measures that monitor
treaty compliance, including reciprocal inspection visits to suspected
bioweapons facilities. This is an essential component of modern
arms-control regimes, similar to those implemented for nuclear weapons
treaties.

An international group of BWC participants has been convened since
January 1995 to accomplish just that, under the chairmanship of
Ambassador Tibor Toth of Hungary. It carries the ponderous name of
"The Ad Hoc Group of the States Parties to the Convention on the
Prohibition of the Development, Production, and Stockpiling of
Bacteriological (Biological) and Toxin Weapons and on Their
Destruction"--or simply the "Ad Hoc Group." By now the Ad
Hoc Group has met for more than 50 weeks in Geneva. The draft treaty
they have prepared is as ponderous as the group's name: It currently
weighs in at several hundred pages, including an astonishing 1,500
"bracketed" paragraphs--which denote passages where there
continues to be disagreement.

For the moment, progress of the Ad Hoc Group seems depressingly
stalled. Embarrassingly, the United States itself bears a direct
responsibility for many brackets, as it has steadfastly resisted certain
attempts to establish provisions for inspections. The U.S. position is
motivated by a desire to protect the interests of the powerful American
biotechnology sector, which fears that inspection visits may be
intrusive, or used as a pretext for industrial espionage. There has been
limited progress on this front with the release last May of a joint
statement by the Pharmaceutical Research and Manufacturers of America
and the Federation of American Scientists who agreed on
"managed-access" measures in support of verification.

Another sticking point rests on a constitutional issue: It is one
thing for the U.S. government to authorize visits to its own labs and
bases, but can it mandate visits to privately held facilities? Some have
argued that such inspections may require warrants. However, under the
Fourth Amendment, warrants are necessary only if actions rise to the
level of a "search." Federal courts have generally held that
the subject of a search must enjoy an expectation of privacy--but this
standard is stricter for individuals than it is for corporate entities,
particularly for industries that are highly regulated. Moreover, the
Supreme Court has already recognized that valid exceptions exist to the
warrant requirement--for example, for drunk driving, contraband and
immigration documentation--and compliance with a vital international
treaty certainly should qualify as a valid exception.

As the world's remaining superpower, the United States bears a unique
responsibility to take the moral high ground in this process, assuming a
leadership role in support of meaningful weapons treaties that establish
international norms. A way must be found before a singular opportunity
is lost.

Assessing the Terrorist Threat

Biological weapons have been called "the poor man's atom
bomb." By any measure, the economic outlay required to develop
offensive bioweapons capabilities is significantly less than that of a
nuclear program. Less is needed in the way of equipment and
infrastructure. The materials themselves are less rare. And less is
required in the way of specialized knowledge for the biological aspects,
since much of the information can be found in the public domain.
Worldwide, trained microbiologists overwhelmingly outnumber nuclear
physicists. All these aspects tempt not only nations of concern, but
also non-state actors. In fact, it seems far more likely that biological
agents will be used by terrorists than by warring nations. Although the
terrorist use of bioweapons is likely to occur on a reduced scale, it
could have worldwide ramifications under unfavorable circumstances.

Little of real consequence has occurred along these lines, but shots
have been fired across the bow. In a bizarre episode that took place in
September 1984, more than 750 people fell ill with food poisoning in The
Dalles, Oregon. Thankfully, no one died. The cause of the epidemic was
not uncovered by health authorities at the time. But in 1986, Ma Anand
Sheela confessed at trial that she and other followers of the Baghwan
Sri Rajneesh had spread salmonella bacteria, grown on the cult's Oregon
ranch, in salad bars in four restaurants, all in an effort to keep
voters from the polls so as to influence a local election. After serving
two and a half years in federal prison, Sheela was released and deported
to Europe.

Between 1990 and 1995, the well-financed Japanese apocalyptic cult
Aum Shinrikyo launched a repeated series of attacks on civilians using
both biological and chemical weapons. These culminated in the infamous
sarin gas release inside the Tokyo subway system in March 1995, which
left 13 people dead and sent more than 5,000 to the hospital. Before
resorting to toxic gas, the group had reportedly attempted,
unsuccessfully, to mount attacks with biological weapons on at least
nine occasions over a five-year period. Aum Shinrikyo boasted a dozen or
so members with biological training and had even gone so far as to buy a
500,000-acre sheep station in Banjawarn, Australia to serve as a site
for operations and to carry out tests.

The cult worked to develop biological weapons based mainly on
botulinum toxin and anthrax, although some members made an unsuccessful
trip to Zaire to obtain Ebola virus. They also attempted, but failed, to
acquire the rickettsia Coxiella burnetii, which causes Q fever. In their
earliest attempts to carry out biological attacks, members of the cult
sprayed homebrewed botulinum toxin on Tokyo streets, near two American
airbases in Japan and at the Narita International Airport. All of these
attacks failed--most likely because they worked with the wrong strain of
C. botulinum (not ail natural variants yield equal toxicity) and because
their misting device may not have been up to the task. They later
switched to anthrax, releasing spores in Tokyo near the Imperial Palace,
the legislature and a foreign embassy. These tactics again failed,
almost certainly because they used a vaccine strain of B. anthracis. And
again, their spraying device may not have worked as intended.

Does this mean that we should all relax, because using bioweapons
turns out to be harder than the perpetrators thought? Is the terrorist
threat therefore exaggerated, as some have maintained? Those who claim
that biowarfare agents can be brewed in a garage by practically anyone
with a modicum of training may be guilty of overstating the case, but
although there has been no shortage of exaggeration, that doesn't mean
we're off the hook.

A lesson from the Aum Shinrikyo case is that any group bent on
developing offensive bioweapons capabilities must overcome two
significant problems, one biological and the other physical. First, it
must acquire and produce stable quantities of a suitably potent agent.
For a variety of reasons this is not the trivial task that it is
sometimes made out to be. Second, it must have an effective means of
delivering the agent to the intended target. For most, but not all,
bioweapon agents, this translates into solving problems of dispersal.
Programs in both the U.S. and the U.S.S.R. devoted years of effort to
perfecting these aspects.

But who is to say that a terrorist group might not find its own way
to imperfect solutions? After all, a terrorist works under entirely
different constraints. For one thing, there's no requirement for the
dispersal to be very efficient, because bioweapons terror attacks are
highly leveraged. If anthrax were released haphazardly in a major U.S.
city and produced only a handful of cases, the public fear and
disruption that would ensue might alone bring about the intended effect.
Our public health system simply isn't geared up to handle an outbreak of
this kind, which would, for a time, flood emergency rooms. A terrorist
group might also be tempted to finesse the dispersal problem and release
some contagious disease, with the aim of starting an epidemic or even a
worldwide pandemic. Or it might choose to act covertly, perhaps
attacking an economic target, such as crops or livestock, rather than a
human population. There are many different options.

In my opinion, the terrorist threat is very real, and it's about to
get worse. And opinions do count here, because quantitative risk
assessment is a practical impossibility. As with nuclear war, successful
bioweapons attacks are characteristically "low probability, high
consequence" events. The expectation value of the risk is the
product of a very small and a very large number, and such numbers carry
great uncertainty.

The Smallpox Wildcard

All of which brings us to smallpox, the bete noire of bioweapons.
Smallpox is a frequently lethal, highly contagious disease caused by the
variola major vims. By the end of the second millennium, it had killed,
crippled, blinded or disfigured one-tenth of all humankind who ever
lived. In one of the greatest achievements of the 20th century, smallpox
was finally eliminated after a decade-long, worldwide health campaign,
which was launched in 1967 under the auspices of the World Health
Organization (WHO), under the direction of Donald A. Henderson (now the
director of the Center for Civilian Biodefense Studies at Johns Hopkins
University). The last recorded case of smallpox occurred in Somalia in
1977, and the disease was officially declared eradicated in 1980.

Although there is no cure for smallpox, it can be prevented with a
vaccine derived from the vaccinia virus. The U.S. Public Health Service
recommends re-vaccination every 10 years, but since routine vaccination
of the U.S. population ended nearly 25 years ago, few Americans retain
immunity today The current stocks of the vaccine are negligible.
Fortunately, there has been some recent action to correct this state of
affairs. As of last September, the U.S. Centers for Disease Control and
Prevention (CDC) have contracted for a 40-million-dose stockpile of the
vaccine. The first batches of the vaccine are slated to be ready by
2004. However, some public-health scientists have questioned whether
such a "small" stockpile is adequate. In the event of a
simultaneous terrorist attack on several major cities, hundreds of
millions of doses might be required to prevent the disease from
spreading.

Whether terrorists could get access to the smallpox virus is still an
open question. At the end of the heroic WHO campaign frozen stocks of
the variola virus were maintained in trust by two organizations: the CDC
and Vector, the Russian State Research Center of Virology and
Biotechnology in Koltsovo, Novosibirsk, Russia. These stocks were
originally scheduled to be destroyed on December 31, 1993, but this date
has been repeatedly postponed as politicians and health officials debate
the wisdom of retaining or destroying the remaining virus, given the
growing bioweapons threat. For now, the decision has been deferred by
the WHO until 2002. A concern shared by many is whether the Russian
stocks are securely held. Ken Alibek has reported that Biopreparat
secretly prepared smallpox-based bioweapons up until at least 1992,
leading one to wonder how much viable smallpox virus might exist outside
the official Koltsovo depository If any weaponized material or viral
stocks found their way to terrorist organizations, t he consequences
could be disastrous. Simply put smallpox represents a direct threat to
the entire world.

"Black Biology"

Beyond the smallpox scenario, what has people worried is the impact
of modern biotechnology. For better or worse, the world is in the midst
of a stunning revolution in the life sciences. Scientists have already
determined the complete genomic sequences for more than 30 microbes and
even more viruses. The DNA code for the cholera pathogen (Vibrio
cholerae) was recently published, and the genomes of more than 100 other
microorganisms are now being sequenced--including the bacteria that
cause anthrax, plague, dysentery and typhoid. Of course, the new
information is critical for answering fundamental and practical
questions in biology and medicine, and will be put to direct practical
use in a myriad of health-related applications. But what about
"black biology"? Could biotechnology be used to produce a new
generation of biowarfare agents with unprecedented power to destroy? Or
is this just alarmist hype? No one can say for sure, but many molecular
biologists familiar with the relevant technologies seem inclined t o a
pessimistic view.

A key reason for pessimism is the ease with which genetic
manipulations are now accomplished. Back in the summer of 1997, JASON (a
group of primarily academic scientists, which consults on technical
matters for the U.S. government and its agencies) addressed the problem
of next-generation bioweapons threats. The JASON study explored a wide
range of future possibilities open to genetically engineered pathogens,
including some that could be achieved with the current state of the art
and others that are--happily--still some way off. The prospects are
sobering. Both bacteria and viruses may now be engineered to be
qualitatively different from conventional bioweapon agents. In terms of
bioweaponry, this includes imbuing them with such "desirable"
attributes as safer handling, increased virulence, improved ability to
target the host, greater difficulty of detection and easier
distribution.

Several broad classes of unconventional pathogens were identified by
JASON. These include "binary" bioweapons, which, by analogy
with chemical weapons, are two-component systems in which each part is
relatively safe to handle, but which become dealdly in combination, and
"designer" variations on genes, viruses and complete life
forms, including chimeras that mingle existing components. Once gene
therapy becomes a medical reality, the technology that allows the repair
or replacement of defective genes might be subverted to introduce
pathogenic sequences. "Stealth" viruses could be fashioned to
infed the host but remain silent, until activated by a trigger. New
zoonotic agents (those transmissible from animals to people) might be
developed specifically for bioweapon purposes by modifying existing
pathogens to seek human hosts. Finally, detailed knowledge of
biochemical signaling pathways could conceivably be used to create
"designer diseases."

Of course, some of these exotic possibilities seem downright
superfluous given the dangers posed by the current generation of
bioweapon agents. Then again, fusion-based hydrogen bombs seem
superfluous, given the destructive power of fission-based weapons. For
now, even the most rudimentary genetic manipulations could be used to
enhance a bioweapons threat, for example by introducing antibiotic
resistance into a weaponized bacterial strain.

Vaccination Woes

Anyone seeking to "improve" on wildtype anthrax might begin
by introducing antibiotic resistance in the form of a gene for [beta]-lactamase,
which enzymatically destroys penicillin. Such a transformation is rather
straightforward, and similar to the kind of thing done routinely today
in molecular biology labs with non-pathogenic organisms. Disease caused
by a multi-drug- resistant variant of anthrax would essentially be
impossible to treat. Only those with prior immunity, conferred by
vaccination, would stand much chance of survival.

Considerations such as this have helped to motivate the ongoing
campaign to vaccinate all 2.4 million U.S. active and reserve troops
against anthrax. The vaccination process, licensed by the Food and Drug
Administration (FDA), requires a six-dose regimen over an 18-month
period. The modern vaccine is prepared from a cell-free filtrate derived
from an a virulent strain of B. anthracis. By most accounts the current
anthrax vaccine is as safe as, perhaps safer than, typical vaccines,
although every vaccine carries residual risk. This is why the oral (Sabin)
polio vaccine will soon no longer be given to children in the U.S.
Comprehensive vaccination programs have reduced polio to such an extent
that the risk associated with receiving the oral dose, which leads to
paralysis in a minuscule fraction of cases, now outweighs the chance of
getting the disease itself.

Unfortunately, the U.S. military anthrax vaccination program has been
mired in controversy and scandal. Prior to the program, the lone
American company licensed by the FDA to produce anthrax vaccine in the
U.S. was the state-owned Michigan Biologics Products Institute, and it
was in danger of losing its license after inspections raised questions
about potency and sterility of the vaccine. The troubled institute was
bought out by Bioport, a company apparently created solely to take over
its assets and land the lucrative government contract for the military.
The most visible corporate director of Bioport is Admiral William Crowe,
former chairman of the Joint Chiefs of Staff. Bioport thus became the
exclusive purveyor of anthrax vaccine and applied for FDA approval of a
Michigan plant to manufacture more. That approval is still at least six
months out. Meanwhile, existing inventories have dwindled, and the
military is running out of vaccine after administering fewer than half a
million doses (out of 14 million) . As a result, they've had to reduce
monthly inoculations from 75,000 to 14,000 and suspend injections for
all but front-line troops considered at greatest risk.

In Senate hearings held in July 2000, Republican Senator Tim
Hutchison of Arkansas reacted to the situation as follows: "The
terms of the contract relief (between the Department of Defense and
Bioport) reduced the number of dosages to be produced by one half,
charged U.S. taxpayers almost three times as much as originally
negotiated, and provided Bioport an interest-free loan of almost $20
million. I am wondering who negotiated such a contract."

Issues of procurement and safety aside, the most disturbing aspect of
the anthrax-vaccination program is the unknown efficacy of the new
vaccine. A limited study, completed back in 1962 among mill workers
handling animal materials, demonstrated protection against the cutaneous
form of anthrax for an earlier version of vaccine. However, no one is
yet prepared to say whether the current formulation will provide
adequate immunity against acute inhalation anthrax produced by a
bioweapon. We may never really know, given the obvious ethical
considerations of experimenting with the vaccine. It also seems possible
that a strain of anthrax might be genetically engineered to circumvent
the immunity conferred by the present vaccine. Does it therefore make
sense to vaccinate all our military personnel? Well, perhaps not all,
but the risks to frontline troops are very real, and the long interval
required for the full immunization schedule demands foresight. In the
end, one is left to make informed guesses.

The difficulties with the anthrax vaccine highlight an endemic
problem: The U.S. has precious little in the way of vaccine production
capabilities, and obtaining FDA approval for a new vaccine protocol
requires at least two years, generally more. The vaccine industry faces
serious issues analogous to the "orphan drug" situation in the
pharmaceutical industry. If a lot of people are not dying of the
disease, where is the market for the product? And how does a
manufacturer protect itself from ruinous lawsuits? This is a topic that
might be better addressed by the public rather than the private sector.

Prospects

The Clinton administration has allocated some $1.4 billion during
fiscal 2000 to combat biological and chemical terrorism, a figure that
has provoked sharp criticism in some quarters. But this number
absolutely pales in comparison with the amount spent annually on
maintaining U.S nuclear capability, which is at least 30-fold greater.
It makes eminent sense to develop improved capability against bioweapons
threats, and we should not have to wait for the biological equivalent of
Hi roshima to rally our defenses.

There are also indirect benefits associated with such an
investment--ones that nuclear spending certainly can't claim to match.
Money spent on research to develop new types of sensitive detectors and
related monitors for biowarfare agents will almost certainly carry over
to the public-health sector in the form of rapid, improved diagnostics
for disease. Money spent on coordinating and developing emergency
response teams at federal, state and local levels will also establish
better mechanisms for dealing with natural outbreaks of emerging
diseases. Money spent on innovative surveillance approaches for
detecting biowarfare attacks should also improve medical epidemiology.
Money spent on vaccine research and delivery may help to buttress our
limited capacity to protect the civilian, as well as the military,
population. And money spent on stockpiling and positioning depots of
smallpox vaccine may turn out to be the smartest hedge-bet of all.

Since 1945, a great many physicists have taken up the challenges
posed by nuclear weaponry, and worked hard at both the national and
international level to limit their destructive potential. But with the
notable exception of a few of the old guard, such as Donald Henderson,
Joshua Lederberg and Matthew Meselson, there has been comparatively
little involvement by biologists in bioweapons issues. The case was put
best by author Richard Preston, who wrote:

The community of biologists in the United States has maintained a
kind of hand-wringing silence on the ethics of creating bioweapons--a
reluctance to talk about it with the public, even a disbelief that it's
happening. Biological weapons are a disgrace to biology. The time has
come for top biologists to assert their leadership and speak out, to
take responsibility on behalf of their profession for the existence of
these weapons and the means of protecting the population against them,
just as leading physicists did a generation ago when nuclear weapons
came along. Moral pressure costs nothing and can help; silence is
unacceptable now.

Acknowledgments

The author thanks Jonathan Tucker, Amy Smithson, Jerry Joyce and
assorted members of JASON for comments and helpful discussions.

Steven M. Block is a professor of biological sciences and of applied
physics at Stanford University, and a member of JASON.

Bibliography

Alibek, K. 1998. "Terrorist and intelligence operations:
potential impact on the U.S. economy." Statement before the Joint
Economic Committee, U.S. Congress, May 20, 1998. Available at:
http://www/house.gov/jec/hearings/intell/alibek.htm

Historical incidents involving biological weapons span the globe and
range from relatively modest events, such as salmonella poisoning of
salad bars in The Dalles, Oregon in 1984, to the notorious experiments
by the Japanese military during the 1930s and 1940s, in which many
thousands of Chinese were killed with infectious agents. Not all
historical events are listed here.